1. Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling
- Author
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Toshiyuki Sakai, Yosuke Iizumi, Tadashi Kondo, Kohei Miki, Jiro Toshima, Yui Matsuzawa, Takahiro Hamoya, Kenji Watanabe, Michihiro Mutoh, Takumi Narita, Masami Komiya, Gen Fujii, Keiji Wakabayashi, and Shinji Kishimoto
- Subjects
Male ,Transcriptional Activation ,0301 basic medicine ,Cancer Research ,Carcinogenesis ,Adenomatous Polyposis Coli Protein ,Drug Evaluation, Preclinical ,Artesunate ,Mice, Transgenic ,medicine.disease_cause ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,In vivo ,Cell Line, Tumor ,T Cell Transcription Factor 1 ,medicine ,Animals ,Humans ,Hepatocyte Nuclear Factor 1-alpha ,Intestinal Mucosa ,Nuclear protein ,Promoter Regions, Genetic ,Enhancer ,Wnt Signaling Pathway ,Cell Nucleus ,Chemistry ,Wnt signaling pathway ,General Medicine ,Gene Expression Regulation, Neoplastic ,Disease Models, Animal ,ran GTP-Binding Protein ,030104 developmental biology ,Adenomatous Polyposis Coli ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Mutation ,Ran ,Cancer research ,Signal transduction - Abstract
Artesunate (ART) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive agents in our drug screening system. Here, we aimed to understand the suppressive effects of ART on intestinal tumorigenesis. In vitro, ART reduced T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter transcriptional activity. In vivo, ART inhibited intestinal polyp development. We found that ART reduces TCF1/TCF7 nuclear translocation by binding the Ras-related nuclear protein (RAN), suggesting that ART inhibits TCF/LEF transcriptional factor nuclear translocation by binding to RAN, thereby inhibiting Wnt signaling. Our results provide a novel mechanism through which artesunate inhibits intestinal tumorigenesis.
- Published
- 2020